Gout and Hyperuricemia Flashcards
Gout is
Hyperuricemia + recurrent attacks of acute arthritis
Define hyperuricemia
Serum uric acid >7 in men and >6 in women
Acute arthritis caused by
Deposition of monosodium urate crystals in joints
Gout leads to
Pain, joint destruction and loss of function
Define Uric Acid nephrolithiasis
Kidney stones of uric acid
Define Tophi
Depositis of monosodium urate crystals in soft tissues of the body -> joint destruction and nerve compression and deformity
Gout Epidemiology
Males
Increases with age
Incidence in women after menopause
Serum urate concentration correlates with
Males Age Body weight obesity Renal insufficiency Alcohol intake Genetics Lead exposure
Xanthine oxidase
Reduces hypothanthine to xanthine to uric acid
Urate is the
predominate species of uric acid in plasma
Hyperuricemia causes
Diet
Overproduced by increased breakdown of nucleic acids (cancer)
Increased cytotoxic drugs
Genetics
Genetics
Overactivity of PRPP synthetase (purine accumulation) HGPRT deficiency (accumulation of PRPP)
PRPP Synthetase
Superactive PRPP leads to excessive purine
Five genetic mutations associated with superactivity
HGPRT deficiency
Involved in purine salvage pathway
Usually takes purines and makes monophosphates but deficiency = more to uric acid
Other causes of Hyperuricemia
Underexcretion
Renal elimination/reabsorption
Joint Response to Urate
Local vasodilation, pain, heat, edema, inflammation, tissue damage via IL-1beta
Acute Gouty Arthritis
Sudden onset of sharp/intense pain, erythema, swelling
First attack is usually monoarticular and usually the big toe
When do acute attacks usually occur?
During the night bc water reabsorption from joint space
Uric Acid Nephrolithiasis
Uric acid kidney stones
Excessive urinary excretion
Gouty Nephropathy
Acute leads to acute renal failure
Chronic: protein in the urine
Tophaceous gout
SQ deposits –> late complication
Damage soft tissue and compress nerves
Treatment of Gout
NSAIDS
Corticosteroids
Colchicine
Prophylactic therapy
Allopurinol Febuxostat Rasburicase Pegloticase Probencid Sulfinpyrazone
NSAIDs
Sulindac, Indomethacin, Naproxen
Relief from pain and inflammation
Consider coadmin of PPIs
Corticosteroids Intraarticular
Limited to 1 or 2 joints
Corticosteroids Systemic
Multiple joints
Risk of osteoporosis, HPA suppresion
Colchicine MOA
Inhibits cell division and migration of neutrophils
Decreases their inflam activity
Colchicine
Test question
Relieves acute gout attacks with low benefits to toxicity ratio
Uric Acid Lowering Therapy
Block Uric acid formation
Enhance urate excretion
Enhance Urate elimination
Enhance urate excretion drug
Uricosuric agents
Block Uric acid formation
drugs
Allopurinol or Febuxostat
Enhance Urate elimination drugs
Rasburicase
Pegloticase
Allopurinol
Inhibitor of xanthine oxidase
Feedback inhibition of purine synthesis
NOT with azathioprine
SJS
Febuxostat
Xanthine Oxidase inhibitor
Non-purine
CYP metabolism
Rasburicase
Uricase
Uric acid to allatoin (more soluble)
Antibodies can form against the drug
Pegloticase
Test question
Uricase
Increase excretion and immunogenicity against allatoin
No data on drug interactions
Probenecid
OAT binds to uric acid so no reabsorption can occur
NOT with salicylates
Sulfinpyrazone
Inhibits reabsorption
Longer acting and more potent then probenacid
Higher GI distress
